Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial.
Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial.
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去铁胺对脑出血后恢复轨迹的影响：I-DEF试验的随机后分析。
作者：
关于ICH后的恢复轨迹和长期功能结局的数据有限。大多数ICH试验通常在缺血性卒中后3个月评估结局。ICH去铁胺（i-DEF）试验在从第-7天至6个月随访期结束的预定时间点纵向评估了改良兰金量表（mRS）。我们评估了试验参与者中mRS的轨迹，并检查了去铁胺（DFO）对该轨迹的影响。我们对i-DEF试验进行了事后分析，该试验是一项多中心、随机、安慰剂对照、双盲、无效设计的II期临床试验，基于实际接受的治疗。有利结局定义为mRS 0-2。采用广义线性混合模型评价随时间推移的结局轨迹，以及在调整随机化变量、脑室内出血和ICH位置后，DFO是否改变了轨迹。共有291例受试者纳入分析（145例安慰剂组和146例DFO组）。两组中mRS 0-2的患者比例从第7天至第180天持续增加（主效应模型中时间的相互作用p<0.0001），但DFO治疗有利地改变了轨迹（相互作用p=0.0010）。在第90天和第180天之间，DFO组改善（p=0.0001），而安慰剂组没有显著改善（p=0.3005）。大部分患者在ICH后6个月内持续改善。未来的ICH试验应评估90天后至少6个月的结局。在i-DEF中，去铁胺治疗似乎加速并改变了mRS评估的恢复轨迹。URL：http://www.clinicaltrials.gov。唯一标识符：NCT 02175225
There are limited data on the trajectory of recovery and long-term functional outcomes after ICH. Most ICH trials have conventionally assessed outcomes at 3 months following the footsteps of ischemic stroke. The ICH Deferoxamine (i-DEF) trial assessed modified Rankin Scale (mRS) longitudinally at pre-specified timepoints from day-7 through the end of the 6-month follow-up period. We evaluated the trajectory of mRS among trial participants and examined the effect of deferoxamine (DFO) on this trajectory. We performed a post-hoc analysis of the i-DEF trial, a multicenter, randomized, placebo-controlled, double-blind, futility-design, phase 2 clinical trial, based on the actual treatment received. Favorable outcome was defined as mRS 0-2. A generalized linear mixed model was used to evaluate the outcome trajectory over time, as well as whether the trajectory was altered by DFO, after adjustments for randomization variables, presence of intraventricular hemorrhage and ICH location. A total of 291 subjects were included in analysis (145 placebo and 146 DFO). The proportion of patients with mRS 0-2 continually increased from Day 7 to 180 in both groups (interaction p<0.0001 for time in main effects model), but treatment with DFO favorably altered the trajectory (interaction p=0.0010). Between day 90 and day 180, the DFO group improved (p=0.0001), whereas there was not significant improvement in the placebo arm (p=0.3005). A large proportion of patients continue to improve up to 6 months after ICH. Future ICH trials should assess outcomes past 90 days for a minimum of 6 months. In i-DEF, treatment with deferoxamine seemed to accelerate and alter the trajectory of recovery as assessed by mRS. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02175225